Table 2.

Summary of molecular mechanisms of essential oils’ major constituents in counteracting neuroinflammation and oxidative stress in the brain.

EO Major Constituent	Chemical Structure	Molecular Mechanism	Experimental Model	Drug Preparation	References
β-caryophyllene		↑Nrf2 ↑CB2 ↑TGFβ ↑IL-10 ↑Arg1 ↑CD206 ↑SOD ↑CAT ↑GSH ↓TLR4 ↓iNOS ↓TNF-α ↓IL-1β ↓PGE2	Ischemic stroke in mice, Experimental autoimmune encephalomyelitis mice (multiple sclerosis in vivo model)	Dissolved in olive or corn oil	[9,79,80]
Myrcene		↑Nrf2/Keap1 ↑Autophagy ↑GSH ↑SOD ↑CAT ↓Iba1 (activated microglia) ↓GFAP (activated astrocytes) ↓iNOS ↓COX-2 ↓TNF-α ↓IL-1β ↓IL-6 ↓MMP-9	Rotenone-induced PD in rats	Dissolved in olive oil	[9,83]
Limonene		↑BDNF ↑GSH ↑SOD ↑CAT ↓NF-κB ↓p38 ↓JNK ↓α-Syn ↓Iba1 (activated microglia) ↓GFAP (activated astrocytes) ↓iNOS ↓COX-2 ↓TNF-α ↓IL-1β ↓IL-6	Rotenone-induced PD in rats	Dissolved in olive oil	[87]
Thymol		↑Nrf2/HO-1 ↑SOD ↑GSH ↑CAT ↓TLR4 ↓NLRP3 ↓NF-κB ↓IL-1 ↓TNFα ↓GFAP (activated astrocytes) ↓IL-6 ↓COX-2 ↓iNOS	Glutamate-induced excitotoxicity in rats, Rotenone-induced PD in rats	Dissolved in sunflower oil	[88,89]
Carvacrol		↑TGF-β ↑IL-10 ↑BDNF ↑SOD ↑BBB integrity ↓IFN-γ ↓IL-6 ↓IL-17 ↓NF-κB ↓TLR4 ↓iNOS ↓COX-2 ↓MMP-9 ↓TRPM7	LPS-treated rats, Experimental autoimmune encephalomyelitis, Traumatic brain injury in rats	Dissolved in 0.9% saline solution or 2% Tween 80 or 0.1% DMSO	[90,91,117,118,119]
Eucalyptol		↑Nrf2 ↑SOD ↑GSH-Px ↓NF-κB ↓COX-2 ↓NOS-2 ↓TNFα ↓IL-6 ↓IL-1	Brain injury after subarachnoid hemorrhage in mice, Hyperammonemic rats, Aβ-toxicated PC-12 cells	Dissolved in corn oil	[95,96,97]
Linalool		↑Nrf2/HO-1 ↓NMDA ↓PGE2 ↓NF-κB ↓TNFα ↓IL1β	PC-12 cells treated with Aβ, LPS-induced BV-2, Triple transgenic and Aβ-induced AD mice	Dissolved in PBS or saline solution with 2% Tween 80 and 1% DMSO	[100,104,105,106]
Geraniol		↑Autophagy ↑GSH ↑SOD ↓IL-6 ↓TNFα ↓α-Syn ↓PERK ↓IRE1α ↓ATF6α JAK1/2	Rotenone-toxicated SK-N-SH, Mice fed with high fat diet In silico prediction	Dissolved in saline solution	[111,113,114]
α-Hexylcinnamaldehyde		SRC, VEGFA, EGFR, HSP90AA1, ESR1	I In silico-predicted targets; Docking binding energies ≤ −3.9 kJ/mol	n.a.	[122]
Nerolidol
Hexahydrofarnesyl acetone
Decanal
Dodecanal
α-Asarone		↑PPARγ-Glutamate transporter 1 ↑IL-10 ↑IL-4 ↑Arg1 ↓p-PERK (ER stress) ↓IL-6 ↓TNFα ↓IL-1β ↓iNOS ↓GFAP ↓MCP1 ↓MIP2	Hypoxia-ischemia neonatal rats, HT-22 cells, Spinal cord injury in rats	Dissolved in 0.5% carboxymethylcellulose	[125,126,128]
β-Asarone		↑PI3K/Akt/Nrf2 ↑HO-1 ↑SOD ↑CAT ↑GSH-Px ↓TNFα (promoter DNA methylation) ↓JNK/c-JUN ↓RELA (NF-κB subunit)	Scratch-injured primary cortical mice neurons, Aβ-treated PC-12 cells, Vascular dementia mice	Dissolved in DMSO or 0.9% saline solution	[129,130,131]

↑: increase; ↓: decrease; n.a.: not available.